Wound healing is an instant response to a wound which repairs damaged lesions and restores dermal structure and function. Wound healing progresses from hemostasis, inflammation and proliferation to tissue remodeling. During human skin wound healing, a critical rate-limiting step is the initiation of the resident epidermal and dermal cells at the wound edge to migrate into the wound bed. The formation of granulation tissue in an open wound allows the re-epithelialization phase to take place, as epithelial cells migrate across the new tissue to form a barrier between the wound and the environment. Basal keratinocytes from the wound edges and dermal appendages such as hair follicles, sweat glands and sebacious (oil) glands are the main cells responsible for the epithelialization phase of wound healing. They advance in a sheet across the wound site and proliferate at its edges, ceasing movement when they meet in the middle. Human keratinocytes (HKCs) laterally migrate across the wound bed from the cut edge to eventually close the wound, the process known as re-epithelialization. The dermal cells, including dermal fibroblasts (DFs) and dermal microvascular endothelial cells (HDMECs), start to move into the wound following the HKC migration where these cells deposit matrix proteins, contract and remodel the newly closed wound and build new blood vessels. Fibroblast cells, located in the dermal layer, play important roles in wound healing by, for example, producing components of the extracellular matrix like collagen and various cytokines, which, in turn, enhance the proliferation and migration of keratinocytes.
Interleukin (IL)-19, a member of the IL-10 cytokine family, which includes IL-10, IL-19, IL-20, IL-22, IL-24, IL-26, IL-28 and IL-29, is expressed in epithelial cells, endothelial cells and macrophages. IL-19 dose-dependently upregulates IL-4 and downregulates IFN-γ, which suggests that IL-19 alters the balance of Th1 and Th2 cells in favor of Th2 cells. IL-19 expression is also correlated with Th2 cytokine production in patients with uremia. IL-19 was induced along with IL-6 and TNF-α after cardiac surgery with a cardiopulmonary bypass (CPB) (Hsing C H, Hsieh M Y, Chen W Y, Cheung So E, Cheng B C, Chang M S. Induction of interleukin-19 and interleukin-22 after cardiac surgery with cardiopulmonary bypass. The Annals of thoracic surgery. 2006; 81: 2196-201). Acutely induced IL-19 in systemic inflammation may promote lung and tissue injury in mice undergoing endotoxic shock (Hsing C H, Chiu C J, Chang L Y, Hsu C C, Chang M S. IL-19 is involved in the pathogenesis of endotoxic shock. Shock 2008; 29:7-15). IL-19 also controls antigen-presenting cells in the lungs and airway responses to microbial products. It was recently reported that IL-19 receptor signaling downregulates antigen-specific T cell responses. IL-19 reduces T-cell responses and promotes the regulatory activity of CD4+ T cells. In patients undergoing coronary artery bypass grafting (CABG) with a CPB, induced IL-19 contributes to cell-mediated immunosuppression. IL-19 promotes breast cancer progression by inducing proinflammatory mediators. IL-19 has multiple functions in immune regulation and disease, and the immunomodulatory role of IL-19 is emerging in psoriasis and chronic inflammatory disorders in general. It has been previously shown that IL-19 expression was seen in basal and suprabasal keratinocytes in a continuous pattern, and was increased in psoriatic epidermis (Li H H, Lin Y C, Chen P J, Hsiao C H, Lee J Y, Chen W C, et al. Interleukin-19 upregulates keratinocyte growth factor and is associated with psoriasis. Br J Dermatol. 2005; 153:591-5). In addition, IL-19 upregulated the expression of KGF in CD8+ T cells (Li H H, Lin Y C, Chen P J, Hsiao C H, Lee J Y, Chen W C, et al. Interleukin-19 upregulates keratinocyte growth factor and is associated with psoriasis. Br J Dermatol. 2005; 153:591-5), which suggested that IL-19 is involved in the proliferation of keratinocytes in psoriasis. However, Davis P A et al. concluded that CD8(+) lymphocytes downregulates wound healing (Davis P A, Corless D J, Aspinall R, Wastell C. Effect of CD4(+) and CD8(+) cell depletion on wound healing. The British journal of surgery. 2001; 88:298-304). Therefore, even if IL-19 upregulated the expression of KGF in CD8+ T, it cannot promote wound healing.
U.S. Pat. No. 5,045,887 relates to healing an external wound of a mammal by administering a composition containing purified platelet-derived growth factor and purified interleukin-1 or administering a composition containing purified insulin-like growth factor and interleukin-1. U.S. Pat. No. 5,202,118 provides wound healing compositions comprising IL-1-alpha and IL-1-beta. U.S. Pat. No. 6,001,357 provides a method of enhancing healing of a wound wherein said wound is caused by cutting, piercing, abrasion, surgical incision, ulceration, thermal burn, chemical burn, radiation burn or friction burn, comprising administering to a mammal in need thereof an amount of anti-IL-5 antibody into a wound site sufficient to result in healing of said wound.
Although there are prior art references disclosing relationship between the members of interleukin family and wound healing, none of them is relevant to the IL-10 cytokine family. The correlation of the IL-10 cytokine family with wound healing remains unclear.